The effects of nitrofuran derivatives on hepatic microsomal mixed-function oxidase activity in rats

Abstract

The effects of four nitrofuran antibacterial food additives and animal drugs were studied on the mixed-function oxidase activity in rat hepatic microsomes. Dietary administration (0.03 to 0.3%) of the compounds for 7 days to Wistar male rats, produced varying degrees of liver enlargement and some compounds exhibited a reducing effect on cytochrome P -450 concentrations and NADPH-cytochrome c reductase activity in hepatic microsomes. The activity of aminopyrine N -demethylase and aniline hydroxylase was affected in varying ways by these compounds. Among these, 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide(furylfuramide) was most potent in increasing the liver weight and in reducing the activity of these microsomal enzymes. In male rats fed a 0.1% furylfuramide-containing diet, the cytochrome P -450 concentration and the activity of aminopyrine N -demethylase and aniline hydroxylase were markedly reduced throughout the experimental period up to 29 days, while cytochrome b 5 and the activity of NADPH-cytochrome c reductase were not changed so markedly. Similar results were also obtained in female rats fed the furylfuramide diet for 3 days, but the reduction in enzyme activities was smaller than that in male rats. Dietary administration of furylfuramide for 3 days to phenobarbital- or 3-methylcholanthrene-pretreated female rats resulted in a marked decrease in the activity of the microsomal enzymes. The pentobarbital sleeping time was prolonged by 57% in male rats fed a 0.1% furylfuramide diet for 7 days. The incubation in vitro of furylfuramide (0.05 m m ) with microsomes from livers of nontreated male rats resulted in decreased activity of aminopyrine N -demethylase and aniline hydroxylase.